New Model of How ADHD Meds Work

By Rick Nauert PhD Senior News Editor

New research has helped scientists understand how medications for attention deficit hyperactivity disorder (ADHD) influence the brain’s reward system.
The new model makes it possible to understand the effect of the medicine and perhaps in the longer term to improve the development of medicine and dose determination.
Authorities report that 3 to 7 percent of school-aged children have ADHD, with ADHD diagnosis’ increasing an average of 3 percent per year from 1997 to 2006 and an average of 5.5 percent per year from 2003 to 2007.
Therefore, it is crucial to know how the medicine works.
Scientists from the University of Copenhagen have developed a new mathematical model of a tiny part of the brain region that registers reward and punishment. When reward and punishment signals run through the brain, the chemical dopamine is always involved.
In the brain, dopamine contributes to series of processes that control our behavior. Actions such as eating, winning a competition, having sex or taking a narcotic drug increase dopamine release. Scientists think that dopamine helps motivate us to repeat actions that have previously been associated with reward.
“It has been discussed for years whether treating ADHD with Ritalin and similar drugs affects the reward system to any significant degree, simply because the dosage given to patients is so low.
“We are the first to show that some components of the dopamine signalling pathways are extremely sensitive to drugs like Ritalin. We have also developed a unified theory to describe the effect of such drugs on the dopamine signal,” said Jakob Kisbye Dreyer, at the Department of Neuroscience and Pharmacology, University of Copenhagen.
Dreyer believes it is vital to know exactly what happens during treatment with drugs like Ritalin. The knowledge will help researchers develop better and more targeted medicine, as well as to understand the psychology underlying ADHD.
Psychologists have known that the actions of human beings are motivated by an unconscious calculation of cost relative to expected gain. In the new research, findings suggest ADHD medicine specifically reduces signals about anticipated punishment.
“Control mechanisms in the brain help keep the dopamine signal in balance so we can register the tiny deviations that signal reward and punishment. We discovered while trying to describe these control mechanisms that our model can be used to examine the influence of Ritalin, for example, on the signal.
“Suddenly we could see that different pathways of the reward system are affected to different degrees by the medicine, and we could calculate at what dosage different parts of the signal would be changed or destroyed,” said Dreyer.
Paradoxically, drugs such as Ritalin can have enigmatic effects: high dosage increases the patient’s activity while low dosage reduces it. This characteristic adds to the challenge of finding the right dosage for a patient.
“We can explain this double effect using our theory. The dopamine signal in the part of the brain that controls our motor behavior is only affected at a higher dose that the dose usually prescribed for treatment.
“Also, our model shows that the threshold between a clinically effective dose and too high a dose is very low. That may explain why the small individual differences between patients have a big impact on treatment.”
Researchers hope that the new model will help doctors determine the correct dose for each patient. Furthermore, the knowledge can help us understand what signals in the brain affect not only ADHD, but schizophrenia, Parkinson’s disease and drug abuse as well.
The study is found in the Journal of Neurophysiology

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